HRP20010059A2 - Isoquinolines as urokinase inhibitors - Google Patents

Info

Publication number

HRP20010059A2

HRP20010059A2 HR20010059A HRP20010059A HRP20010059A2 HR P20010059 A2 HRP20010059 A2 HR P20010059A2 HR 20010059 A HR20010059 A HR 20010059A HR P20010059 A HRP20010059 A HR P20010059A HR P20010059 A2 HRP20010059 A2 HR P20010059A2

Authority

HR

Croatia

Prior art keywords

isoquinolinyl

guanidino

mmol

chloro

sulfonyl

Prior art date

1998-07-24

Links

• Espacenet
• Global Dossier
• Discuss

• 239000002797 plasminogen activator inhibitor Substances 0.000 title description 8
• 150000002537 isoquinolines Chemical class 0.000 title description 3
• -1 het Chemical group 0.000 claims description 238
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 134
• 150000001875 compounds Chemical class 0.000 claims description 107
• 150000003839 salts Chemical class 0.000 claims description 85
• 238000002360 preparation method Methods 0.000 claims description 82
• 229910052757 nitrogen Inorganic materials 0.000 claims description 80
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 67
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 64
• 239000000460 chlorine Substances 0.000 claims description 58
• 229920006395 saturated elastomer Polymers 0.000 claims description 46
• 238000000034 method Methods 0.000 claims description 43
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 34
• 125000001424 substituent group Chemical group 0.000 claims description 31
• ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 28
• 238000006243 chemical reaction Methods 0.000 claims description 28
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 27
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 22
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 21
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
• 125000000217 alkyl group Chemical group 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 19
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical group C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 14
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
• 229910052801 chlorine Inorganic materials 0.000 claims description 13
• OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical class C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 claims description 13
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 12
• 125000002947 alkylene group Chemical group 0.000 claims description 12
• 229910052794 bromium Chemical group 0.000 claims description 12
• 239000003153 chemical reaction reagent Substances 0.000 claims description 12
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 12
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 230000008569 process Effects 0.000 claims description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• CXDHJGCWMIOAQP-UHFFFAOYSA-N 2-pyridin-3-yl-1,4,5,6-tetrahydropyrimidine;hydrochloride Chemical compound Cl.C1CCNC(C=2C=NC=CC=2)=N1 CXDHJGCWMIOAQP-UHFFFAOYSA-N 0.000 claims description 10
• IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims description 10
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• FKLXTEJVWZKEGC-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCCC1 FKLXTEJVWZKEGC-UHFFFAOYSA-N 0.000 claims description 7
• MWEYSFQTTAFUFL-GFCCVEGCSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(O)=O MWEYSFQTTAFUFL-GFCCVEGCSA-N 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
• 239000005977 Ethylene Substances 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 238000011282 treatment Methods 0.000 claims description 5
• LNUBQTYRTKJZLL-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(oxan-2-yloxy)ethyl]amino]cyclopentane-1-carboxylic acid Chemical class C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(C1(CCCC1)C(O)=O)CCOC1CCCCO1 LNUBQTYRTKJZLL-UHFFFAOYSA-N 0.000 claims description 4
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 4
• 125000000732 arylene group Chemical group 0.000 claims description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
• 150000001409 amidines Chemical class 0.000 claims description 3
• 239000002585 base Substances 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 3
• BMEATRFQZUKHQA-MRXNPFEDSA-N tert-butyl (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpiperidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@H]1CCCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 BMEATRFQZUKHQA-MRXNPFEDSA-N 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
• BRGLJXKRORUYFU-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-(2-methoxyethyl)cyclopentane-1-carboxamide Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)NCCOC)CCCC1 BRGLJXKRORUYFU-UHFFFAOYSA-N 0.000 claims description 2
• WGQAIRAOZLFUSH-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylic acid Chemical class C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCCCC1 WGQAIRAOZLFUSH-UHFFFAOYSA-N 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
• 125000004976 cyclobutylene group Chemical group 0.000 claims description 2
• 125000004977 cycloheptylene group Chemical group 0.000 claims description 2
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000004979 cyclopentylene group Chemical group 0.000 claims description 2
• 239000012458 free base Substances 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 101100133350 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nhp-1 gene Proteins 0.000 claims 2
• 229910052698 phosphorus Inorganic materials 0.000 claims 2
• SFSCYVUZGPRXIE-CYBMUJFWSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpiperidine-2-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCCC[C@@H]1C(O)=O SFSCYVUZGPRXIE-CYBMUJFWSA-N 0.000 claims 1
• OXLQLJKXSBVAFG-UHFFFAOYSA-N 1-[[4-bromo-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylic acid Chemical compound C=1C=C2C(Br)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(O)=O)CCCC1 OXLQLJKXSBVAFG-UHFFFAOYSA-N 0.000 claims 1
• LIPQMUVUZWSFOR-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylic acid Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(O)=O)CCCC1 LIPQMUVUZWSFOR-UHFFFAOYSA-N 0.000 claims 1
• OGLMCCZSIWUXDA-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-(2-hydroxyethyl)-n-methylcyclopentane-1-carboxamide Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)N(CCO)C)CCCC1 OGLMCCZSIWUXDA-UHFFFAOYSA-N 0.000 claims 1
• DEPFCMSTRPLWNG-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclobutane-1-carboxylic acid Chemical class C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCC1 DEPFCMSTRPLWNG-UHFFFAOYSA-N 0.000 claims 1
• UGFABUVNULNZNU-UHFFFAOYSA-N 2-[4-chloro-7-[[1-(morpholine-4-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(=O)N2CCOCC2)CCCC1 UGFABUVNULNZNU-UHFFFAOYSA-N 0.000 claims 1
• XSDAXWRCPTYNOD-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2-methylpropanoic acid Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NC(C)(C)C(O)=O)=CC=C21 XSDAXWRCPTYNOD-UHFFFAOYSA-N 0.000 claims 1
• ZHHDLYHTFLCWAS-UHFFFAOYSA-N 4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]oxane-4-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCOCC1 ZHHDLYHTFLCWAS-UHFFFAOYSA-N 0.000 claims 1
• 238000006073 displacement reaction Methods 0.000 claims 1
• 239000000825 pharmaceutical preparation Substances 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 409
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 340
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 335
• 239000000243 solution Substances 0.000 description 307
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 225
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 221
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 207
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 172
• 239000007787 solid Substances 0.000 description 171
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 168
• 235000019439 ethyl acetate Nutrition 0.000 description 168
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 138
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 122
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 121
• 239000003480 eluent Substances 0.000 description 114
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 110
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 105
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 100
• 238000010898 silica gel chromatography Methods 0.000 description 99
• 239000002904 solvent Substances 0.000 description 93
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 84
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 80
• 229960000789 guanidine hydrochloride Drugs 0.000 description 79
• 239000012267 brine Substances 0.000 description 78
• 229910000104 sodium hydride Inorganic materials 0.000 description 78
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 77
• 239000006185 dispersion Substances 0.000 description 72
• 239000002480 mineral oil Substances 0.000 description 71
• 235000010446 mineral oil Nutrition 0.000 description 71
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 65
• 239000002244 precipitate Substances 0.000 description 63
• 239000000284 extract Substances 0.000 description 60
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 60
• 239000000725 suspension Substances 0.000 description 55
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 53
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
• 239000011541 reaction mixture Substances 0.000 description 52
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
• 235000002639 sodium chloride Nutrition 0.000 description 51
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 50
• 235000019341 magnesium sulphate Nutrition 0.000 description 50
• UVTOICZCRRXFKE-UHFFFAOYSA-N 1,4-dichloroisoquinoline-7-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2C(Cl)=CN=C(Cl)C2=C1 UVTOICZCRRXFKE-UHFFFAOYSA-N 0.000 description 49
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 40
• 238000001914 filtration Methods 0.000 description 37
• QVDYYQXUNAQSNI-UHFFFAOYSA-N ethyl acetate;pentane Chemical compound CCCCC.CCOC(C)=O QVDYYQXUNAQSNI-UHFFFAOYSA-N 0.000 description 32
• 239000000843 powder Substances 0.000 description 32
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 29
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 27
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 26
• 235000017557 sodium bicarbonate Nutrition 0.000 description 26
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
• DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 26
• 238000010992 reflux Methods 0.000 description 25
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
• 239000000741 silica gel Substances 0.000 description 23
• 229910002027 silica gel Inorganic materials 0.000 description 23
• 239000006260 foam Substances 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• 238000004587 chromatography analysis Methods 0.000 description 18
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
• 239000000047 product Substances 0.000 description 18
• 239000000126 substance Substances 0.000 description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
• 239000012074 organic phase Substances 0.000 description 16
• SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 16
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
• 239000006196 drop Substances 0.000 description 14
• 229940012957 plasmin Drugs 0.000 description 14
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• 238000001665 trituration Methods 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 12
• 239000000463 material Substances 0.000 description 12
• 229960005356 urokinase Drugs 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• 238000001556 precipitation Methods 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
• 239000003513 alkali Substances 0.000 description 10
• 238000002425 crystallisation Methods 0.000 description 10
• 230000008025 crystallization Effects 0.000 description 10
• 238000001704 evaporation Methods 0.000 description 10
• 230000008020 evaporation Effects 0.000 description 10
• 229960004198 guanidine Drugs 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 239000007864 aqueous solution Substances 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 235000015320 potassium carbonate Nutrition 0.000 description 9
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 239000006071 cream Substances 0.000 description 8
• 230000007062 hydrolysis Effects 0.000 description 8
• 238000006460 hydrolysis reaction Methods 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• 238000005406 washing Methods 0.000 description 8
• ZCCHALYUTAVUSN-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]acetic acid Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)NCC(=O)O)=CC=C21 ZCCHALYUTAVUSN-UHFFFAOYSA-N 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 7
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000012230 colorless oil Substances 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 238000010511 deprotection reaction Methods 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 239000004474 valine Substances 0.000 description 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• 206010028980 Neoplasm Diseases 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 6
• 235000019270 ammonium chloride Nutrition 0.000 description 6
• 239000000538 analytical sample Substances 0.000 description 6
• 230000033115 angiogenesis Effects 0.000 description 6
• 210000004027 cell Anatomy 0.000 description 6
• 238000004440 column chromatography Methods 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000012452 mother liquor Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 230000029663 wound healing Effects 0.000 description 6
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
• YRRBJVJOEBRPNJ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(4-methoxyphenyl)methyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 YRRBJVJOEBRPNJ-UHFFFAOYSA-N 0.000 description 5
• SOBOKMKYKONTMQ-UHFFFAOYSA-N 2-[benzyl-[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]acetic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)N(CC(O)=O)CC1=CC=CC=C1 SOBOKMKYKONTMQ-UHFFFAOYSA-N 0.000 description 5
• YQZBRWHIONZQHW-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]propanoic acid Chemical compound C1=C(C(=O)NCCC(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 YQZBRWHIONZQHW-UHFFFAOYSA-N 0.000 description 5
• 102000001938 Plasminogen Activators Human genes 0.000 description 5
• 108010001014 Plasminogen Activators Proteins 0.000 description 5
• 208000027418 Wounds and injury Diseases 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 229940127126 plasminogen activator Drugs 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 230000007838 tissue remodeling Effects 0.000 description 5
• 210000004881 tumor cell Anatomy 0.000 description 5
• PPAGQIPDYXUSCR-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n,n-dimethylcyclopentane-1-carboxamide Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)N(C)C)CCCC1 PPAGQIPDYXUSCR-UHFFFAOYSA-N 0.000 description 4
• FOEVXJQCBZWDAH-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carbonyl chloride Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(Cl)=O)CCCC1 FOEVXJQCBZWDAH-UHFFFAOYSA-N 0.000 description 4
• KCDBAKVYEZZRTJ-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCCC1 KCDBAKVYEZZRTJ-UHFFFAOYSA-N 0.000 description 4
• ZXCUCSAPANYTAE-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(cyclopentylmethyl)amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1CCCC1 ZXCUCSAPANYTAE-UHFFFAOYSA-N 0.000 description 4
• OBEVLDNMRHPDRP-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(3-methoxyphenyl)methyl]amino]acetic acid Chemical compound COC1=CC=CC(CN(CC(O)=O)S(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)=C1 OBEVLDNMRHPDRP-UHFFFAOYSA-N 0.000 description 4
• NDLXLLJSLDEOHD-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]acetic acid Chemical compound C1=C(S(=O)(=O)NCC(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 NDLXLLJSLDEOHD-UHFFFAOYSA-N 0.000 description 4
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 4
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 201000004681 Psoriasis Diseases 0.000 description 4
• 208000025865 Ulcer Diseases 0.000 description 4
• 206010052428 Wound Diseases 0.000 description 4
• RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• OJEYDZBIAYMFFD-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1C[CH]CC1 OJEYDZBIAYMFFD-UHFFFAOYSA-N 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
• 210000002744 extracellular matrix Anatomy 0.000 description 4
• XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• BHIWKHZACMWKOJ-UHFFFAOYSA-N isobutyric acid methyl ester Natural products COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 235000017550 sodium carbonate Nutrition 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 230000009466 transformation Effects 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 231100000397 ulcer Toxicity 0.000 description 4
• XOXPBLZIYAGQII-OAHLLOKOSA-N (2R)-2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]-2-phenylacetic acid Chemical compound ClC1=NC=C(C2=CC=C(C=C12)C(=O)N[C@H](C1=CC=CC=C1)C(=O)O)Cl XOXPBLZIYAGQII-OAHLLOKOSA-N 0.000 description 3
• HXYHJMSSTIKIBW-UHFFFAOYSA-N 1,4-dichloro-n-[1-(hydroxymethyl)cyclopentyl]isoquinoline-7-sulfonamide Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(CO)CCCC1 HXYHJMSSTIKIBW-UHFFFAOYSA-N 0.000 description 3
• NYYSTELLMIKOJD-UHFFFAOYSA-N 1,4-dichloroisoquinoline-7-carbonyl chloride Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)Cl)=CC=C21 NYYSTELLMIKOJD-UHFFFAOYSA-N 0.000 description 3
• JAJNPJRKZCIKSX-UHFFFAOYSA-N 1-[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)N1CCCC1C(O)=O JAJNPJRKZCIKSX-UHFFFAOYSA-N 0.000 description 3
• DODYLCNGEVXWSK-UHFFFAOYSA-N 1-[[4-bromo-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C(Br)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(O)=O)CCCC1 DODYLCNGEVXWSK-UHFFFAOYSA-N 0.000 description 3
• KVBLKZYVEMXXAR-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(O)=O)CCCC1 KVBLKZYVEMXXAR-UHFFFAOYSA-N 0.000 description 3
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• BPIQTAJUHXPPEI-UHFFFAOYSA-N 2-(n-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylanilino)acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)C1=CC=CC=C1 BPIQTAJUHXPPEI-UHFFFAOYSA-N 0.000 description 3
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
• QZUILIMUYMWYNZ-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]acetic acid Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NCC(=O)O)=CC=C21 QZUILIMUYMWYNZ-UHFFFAOYSA-N 0.000 description 3
• COZYKIRLXOENRO-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]butanedioic acid Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NC(CC(=O)O)C(O)=O)=CC=C21 COZYKIRLXOENRO-UHFFFAOYSA-N 0.000 description 3
• GZWRFKISPFGGPQ-UHFFFAOYSA-N 2-[(2-methoxyphenyl)methylazaniumyl]acetate Chemical compound COC1=CC=CC=C1CNCC(O)=O GZWRFKISPFGGPQ-UHFFFAOYSA-N 0.000 description 3
• FSHQMEULJGMJPU-UHFFFAOYSA-N 2-[(2-methylphenyl)methylazaniumyl]acetate Chemical compound CC1=CC=CC=C1CNCC(O)=O FSHQMEULJGMJPU-UHFFFAOYSA-N 0.000 description 3
• OGPDDYUQRFSYEJ-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methylazaniumyl]acetate Chemical compound COC1=CC=CC(CNCC(O)=O)=C1 OGPDDYUQRFSYEJ-UHFFFAOYSA-N 0.000 description 3
• LDGLKBHAODXSMN-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methyl-methylamino]-2-phenylacetic acid Chemical compound C=1C=C2C(Cl)=CN=C(N=C(N)N)C2=CC=1CN(C)C(C(O)=O)C1=CC=CC=C1 LDGLKBHAODXSMN-UHFFFAOYSA-N 0.000 description 3
• DUSOHEUFUBHXJJ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(cyclohexylmethyl)amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1CCCCC1 DUSOHEUFUBHXJJ-UHFFFAOYSA-N 0.000 description 3
• CZCOGZKCUPMCRK-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-3-ylmethyl)amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CN=C1 CZCOGZKCUPMCRK-UHFFFAOYSA-N 0.000 description 3
• LKTWTXYOQVQUKL-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-4-ylmethyl)amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=NC=C1 LKTWTXYOQVQUKL-UHFFFAOYSA-N 0.000 description 3
• AQDSGSGLHSNIJL-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(2-methoxyphenyl)methyl]amino]acetic acid Chemical compound COC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 AQDSGSGLHSNIJL-UHFFFAOYSA-N 0.000 description 3
• NKVFMISXWFCPTO-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(2-methylphenyl)methyl]amino]acetic acid Chemical compound CC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 NKVFMISXWFCPTO-UHFFFAOYSA-N 0.000 description 3
• NDVJUKSYUQLKAO-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(3-chlorophenyl)methyl]amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC(Cl)=C1 NDVJUKSYUQLKAO-UHFFFAOYSA-N 0.000 description 3
• JHSASXLTXXRGRH-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-2-phenylacetic acid Chemical compound C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1C(=O)NC(C(O)=O)C1=CC=CC=C1 JHSASXLTXXRGRH-UHFFFAOYSA-N 0.000 description 3
• RVVUYQLRIURYNP-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)NC(C(O)=O)CC1=CC=CC=C1 RVVUYQLRIURYNP-UHFFFAOYSA-N 0.000 description 3
• QZWRFXOWKXMZHZ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-4-methylpentanoic acid Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(C(=O)NC(CC(C)C)C(O)=O)=CC=C21 QZWRFXOWKXMZHZ-UHFFFAOYSA-N 0.000 description 3
• ISCSYIIAJTXZIG-UHFFFAOYSA-N 2-[benzyl-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC=C1 ISCSYIIAJTXZIG-UHFFFAOYSA-N 0.000 description 3
• GRYUAOWKPXQBSM-UHFFFAOYSA-N 2-[benzyl-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methyl]amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1CN(CC(O)=O)CC1=CC=CC=C1 GRYUAOWKPXQBSM-UHFFFAOYSA-N 0.000 description 3
• GEAILAYUCGCNKZ-UHFFFAOYSA-N 2-[cyclopentylmethyl-(1,4-dichloroisoquinolin-7-yl)sulfonylamino]acetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(CC(=O)O)CC1CCCC1 GEAILAYUCGCNKZ-UHFFFAOYSA-N 0.000 description 3
• MBXFJGWNDTUZLK-UHFFFAOYSA-N 2-isoquinolin-1-ylguanidine Chemical class C1=CC=C2C(NC(=N)N)=NC=CC2=C1 MBXFJGWNDTUZLK-UHFFFAOYSA-N 0.000 description 3
• FABBVURNVFOHRS-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]propanoic acid Chemical compound C1=C(S(=O)(=O)NCCC(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 FABBVURNVFOHRS-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 206010016654 Fibrosis Diseases 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
• 102000035195 Peptidases Human genes 0.000 description 3
• 108091005804 Peptidases Proteins 0.000 description 3
• 239000004365 Protease Substances 0.000 description 3
• 102000012479 Serine Proteases Human genes 0.000 description 3
• 108010022999 Serine Proteases Proteins 0.000 description 3
• 206010064390 Tumour invasion Diseases 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 230000010072 bone remodeling Effects 0.000 description 3
• 244000309464 bull Species 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 230000009400 cancer invasion Effects 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 230000004709 cell invasion Effects 0.000 description 3
• 238000006731 degradation reaction Methods 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 3
• XDKDVZIQKXUAJE-CZUORRHYSA-N ethyl (1r,2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCC[C@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 XDKDVZIQKXUAJE-CZUORRHYSA-N 0.000 description 3
• JVAIJMJGLRGSCL-CJNGLKHVSA-N ethyl (1r,2s)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]cyclohexane-1-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 JVAIJMJGLRGSCL-CJNGLKHVSA-N 0.000 description 3
• XFVQLLHETIXZAJ-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(C(=O)OCC)CCCC1 XFVQLLHETIXZAJ-UHFFFAOYSA-N 0.000 description 3
• NSWKTIPIBOVPPW-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinoline-7-carbonyl)amino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1C(=O)NC1(C(=O)OCC)CCCC1 NSWKTIPIBOVPPW-UHFFFAOYSA-N 0.000 description 3
• FUXWRQFSCSLVFG-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-methylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(C)C1(C(=O)OCC)CCCC1 FUXWRQFSCSLVFG-UHFFFAOYSA-N 0.000 description 3
• MOLPQBLNDGXPBK-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1C(=O)NC1(C(=O)OCC)CCCC1 MOLPQBLNDGXPBK-UHFFFAOYSA-N 0.000 description 3
• ADFASIQRQWKXSJ-UHFFFAOYSA-N ethyl 1-aminocyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1(N)CCCC1 ADFASIQRQWKXSJ-UHFFFAOYSA-N 0.000 description 3
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 3
• 230000004761 fibrosis Effects 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 238000007327 hydrogenolysis reaction Methods 0.000 description 3
• 210000002865 immune cell Anatomy 0.000 description 3
• 238000002513 implantation Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000008595 infiltration Effects 0.000 description 3
• 238000001764 infiltration Methods 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 210000001161 mammalian embryo Anatomy 0.000 description 3
• 230000001394 metastastic effect Effects 0.000 description 3
• 206010061289 metastatic neoplasm Diseases 0.000 description 3
• USKLNUIACYRUJK-SSDOTTSWSA-N methyl (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]propanoate Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N[C@H](C)C(=O)OC)=CC=C21 USKLNUIACYRUJK-SSDOTTSWSA-N 0.000 description 3
• ODXIYADHPLOJIB-UHFFFAOYSA-N methyl 4-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]oxane-4-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCOCC1 ODXIYADHPLOJIB-UHFFFAOYSA-N 0.000 description 3
• HGBNBQUWANCOJR-UHFFFAOYSA-N methyl 4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]oxane-4-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCOCC1 HGBNBQUWANCOJR-UHFFFAOYSA-N 0.000 description 3
• AZFBPYNPITWILD-UHFFFAOYSA-N methyl 4-aminooxane-4-carboxylate Chemical compound COC(=O)C1(N)CCOCC1 AZFBPYNPITWILD-UHFFFAOYSA-N 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 230000016087 ovulation Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 230000021595 spermatogenesis Effects 0.000 description 3
• PRBFGHIWCWVLRQ-PBHICJAKSA-N tert-butyl (1r,2s)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]cyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 PRBFGHIWCWVLRQ-PBHICJAKSA-N 0.000 description 3
• GSIFMMNNDXIWMR-PBHICJAKSA-N tert-butyl (1r,2s)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 GSIFMMNNDXIWMR-PBHICJAKSA-N 0.000 description 3
• OCDVWGNSUMCOHV-XFULWGLBSA-N tert-butyl (2r)-1-[4-bromo-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@H]1CCCN1S(=O)(=O)C1=CC=C(C(Br)=CN=C2NC(N)=N)C2=C1 OCDVWGNSUMCOHV-XFULWGLBSA-N 0.000 description 3
• JRTCUNBQTYBCDT-UHFFFAOYSA-N tert-butyl 1-(1,4-dichloroisoquinoline-7-carbonyl)pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCCN1C(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 JRTCUNBQTYBCDT-UHFFFAOYSA-N 0.000 description 3
• OGCHZLXCRHPOMZ-UHFFFAOYSA-N tert-butyl 2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 OGCHZLXCRHPOMZ-UHFFFAOYSA-N 0.000 description 3
• LLTUGVPFSXNQMO-UHFFFAOYSA-N tert-butyl 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]-3-[(2-methylpropan-2-yl)oxy]propanoate Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NC(COC(C)(C)C)C(=O)OC(C)(C)C)=CC=C21 LLTUGVPFSXNQMO-UHFFFAOYSA-N 0.000 description 3
• JNDYHOGEYBOCCM-UHFFFAOYSA-N tert-butyl 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]-3-methylbutanoate Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NC(C(C)C)C(=O)OC(C)(C)C)=CC=C21 JNDYHOGEYBOCCM-UHFFFAOYSA-N 0.000 description 3
• ICWWEEXMUFXMQT-UHFFFAOYSA-N tert-butyl 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]-3-phenylpropanoate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1C(=O)NC(C(=O)OC(C)(C)C)CC1=CC=CC=C1 ICWWEEXMUFXMQT-UHFFFAOYSA-N 0.000 description 3
• YYKMONSLEMEASL-UHFFFAOYSA-N tert-butyl 2-[(1,4-dichloroisoquinoline-7-carbonyl)amino]-4-methylpentanoate Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NC(CC(C)C)C(=O)OC(C)(C)C)=CC=C21 YYKMONSLEMEASL-UHFFFAOYSA-N 0.000 description 3
• FQQGCTUIZNXLND-UHFFFAOYSA-N tert-butyl 2-[(4-methoxyphenyl)methylamino]acetate Chemical compound COC1=CC=C(CNCC(=O)OC(C)(C)C)C=C1 FQQGCTUIZNXLND-UHFFFAOYSA-N 0.000 description 3
• HDXMPGOKFMBDHJ-UHFFFAOYSA-N tert-butyl 2-aminobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1N HDXMPGOKFMBDHJ-UHFFFAOYSA-N 0.000 description 3
• MYBNTSLQHDGJFY-UHFFFAOYSA-N tert-butyl 2-anilinoacetate Chemical compound CC(C)(C)OC(=O)CNC1=CC=CC=C1 MYBNTSLQHDGJFY-UHFFFAOYSA-N 0.000 description 3
• NTTOSTKJCKYXMS-UHFFFAOYSA-N tert-butyl 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC(NS(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)=C1 NTTOSTKJCKYXMS-UHFFFAOYSA-N 0.000 description 3
• YGIRNXMYJLWFLH-UHFFFAOYSA-N tert-butyl 3-aminobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC(N)=C1 YGIRNXMYJLWFLH-UHFFFAOYSA-N 0.000 description 3
• 210000004291 uterus Anatomy 0.000 description 3
• 239000008096 xylene Substances 0.000 description 3
• SJEBRBJOSDSFFJ-GGMFNZDASA-N (1r,2s)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N[C@H]1CCCC[C@H]1C(O)=O SJEBRBJOSDSFFJ-GGMFNZDASA-N 0.000 description 2
• CLYYEXAIMZOORP-LBPRGKRZSA-N (2R)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-3,3-dimethylbutanoic acid Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)N[C@H](C(C)(C)C)C(O)=O)=CC=C21 CLYYEXAIMZOORP-LBPRGKRZSA-N 0.000 description 2
• YKFJTIJJLBTWKD-GFCCVEGCSA-N (2R)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-3-methylbutanoic acid Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)N[C@H](C(C)C)C(O)=O)=CC=C21 YKFJTIJJLBTWKD-GFCCVEGCSA-N 0.000 description 2
• MPQOREHNRHHMOB-GFCCVEGCSA-N (2r)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 MPQOREHNRHHMOB-GFCCVEGCSA-N 0.000 description 2
• HYRNCYNDKFUWJR-UTONKHPSSA-N (2r)-1-[1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=CC2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(O)=O HYRNCYNDKFUWJR-UTONKHPSSA-N 0.000 description 2
• NYKNXEDMEAIPCU-UTONKHPSSA-N (2r)-1-[4-bromo-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Br)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(O)=O NYKNXEDMEAIPCU-UTONKHPSSA-N 0.000 description 2
• RRHQRHGBTLXWPQ-CQSZACIVSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-n-(2-hydroxyethyl)pyrrolidine-2-carboxamide Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(=O)NCCO RRHQRHGBTLXWPQ-CQSZACIVSA-N 0.000 description 2
• FYIDKYAWXAKKLQ-BTQNPOSSSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpiperidine-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCCC[C@@H]1C(O)=O FYIDKYAWXAKKLQ-BTQNPOSSSA-N 0.000 description 2
• NMLXXSFWQSUYTC-GFCCVEGCSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxamide Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(N)=O NMLXXSFWQSUYTC-GFCCVEGCSA-N 0.000 description 2
• VVRMPAFFZMVHMH-UTONKHPSSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylpyrrolidine-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1C(O)=O VVRMPAFFZMVHMH-UTONKHPSSA-N 0.000 description 2
• BLOOPJZYRFFEJI-SNVBAGLBSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]butanedioic acid Chemical compound C1=C(S(=O)(=O)N[C@H](CC(O)=O)C(O)=O)C=C2C(N=C(N)N)=NC=C(Cl)C2=C1 BLOOPJZYRFFEJI-SNVBAGLBSA-N 0.000 description 2
• AJASBPFHCRVVKL-FYZOBXCZSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]propanoic acid;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N[C@H](C)C(O)=O)=CC=C21 AJASBPFHCRVVKL-FYZOBXCZSA-N 0.000 description 2
• JHSASXLTXXRGRH-OAHLLOKOSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-2-phenylacetic acid Chemical compound C1([C@H](C(O)=O)NC(=O)C2=CC=C3C(Cl)=CN=C(C3=C2)N=C(N)N)=CC=CC=C1 JHSASXLTXXRGRH-OAHLLOKOSA-N 0.000 description 2
• LGQADKJMGQHVKZ-UHFFFAOYSA-N 1,4-dichloroisoquinoline-7-carboxylic acid Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)O)=CC=C21 LGQADKJMGQHVKZ-UHFFFAOYSA-N 0.000 description 2
• SLXLIRUDSAJOEX-UHFFFAOYSA-N 1-[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]pyrrolidine-2-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)N1CCCC1C(O)=O SLXLIRUDSAJOEX-UHFFFAOYSA-N 0.000 description 2
• FYWPVRJASJZPND-UHFFFAOYSA-N 1-[[4-bromo-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]-2-ethylcyclopentane-1-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.CCC1CCCC1(C(O)=O)N(CCN(C)C)S(=O)(=O)C1=CC=C(C(Br)=CN=C2NC(N)=N)C2=C1 FYWPVRJASJZPND-UHFFFAOYSA-N 0.000 description 2
• AFZDACZZKMGLAU-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(2-hydroxyethyl)amino]-n,n-dimethylcyclopentane-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCO)C1(C(=O)N(C)C)CCCC1 AFZDACZZKMGLAU-UHFFFAOYSA-N 0.000 description 2
• AVIKOFVIWUJCJU-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(oxan-2-yloxy)ethyl]amino]-n,n-dimethylcyclopentane-1-carboxamide Chemical compound C1CCCOC1OCCN(S(=O)(=O)C=1C=C2C(NC(N)=N)=NC=C(Cl)C2=CC=1)C1(C(=O)N(C)C)CCCC1 AVIKOFVIWUJCJU-UHFFFAOYSA-N 0.000 description 2
• PBFXRWVLBFCQCW-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-methylamino]cyclopentane-1-carboxylic acid;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(C)C1(C(O)=O)CCCC1 PBFXRWVLBFCQCW-UHFFFAOYSA-N 0.000 description 2
• IYYRRUPGOBWIJF-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-(2-hydroxyethyl)-n-methylcyclopentane-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)N(CCO)C)CCCC1 IYYRRUPGOBWIJF-UHFFFAOYSA-N 0.000 description 2
• ZWHAXYGLJPNGCY-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-(2-methoxyethyl)cyclopentane-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)NCCOC)CCCC1 ZWHAXYGLJPNGCY-UHFFFAOYSA-N 0.000 description 2
• LDKASNKJBPFBKL-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclobutane-1-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCC1 LDKASNKJBPFBKL-UHFFFAOYSA-N 0.000 description 2
• SIEBWFXRNISWTR-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCCC1 SIEBWFXRNISWTR-UHFFFAOYSA-N 0.000 description 2
• FPRNNZYAUOXVBV-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]cyclopentane-1-carboxylic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)NC1(C(O)=O)CCCC1 FPRNNZYAUOXVBV-UHFFFAOYSA-N 0.000 description 2
• VIWYWRSFQRIVPI-UHFFFAOYSA-N 2,4-ditert-butyl-5-nitrophenol Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=C([N+]([O-])=O)C=C1O VIWYWRSFQRIVPI-UHFFFAOYSA-N 0.000 description 2
• YIHCKZKEKWQDFC-UHFFFAOYSA-N 2-(n-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylanilino)acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)C1=CC=CC=C1 YIHCKZKEKWQDFC-UHFFFAOYSA-N 0.000 description 2
• BTPOPPOVMPRWAI-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[(2-methoxyphenyl)methyl]amino]acetic acid Chemical compound COC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 BTPOPPOVMPRWAI-UHFFFAOYSA-N 0.000 description 2
• JONXVMDKEDXNSM-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[(2-methylphenyl)methyl]amino]acetic acid Chemical compound CC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 JONXVMDKEDXNSM-UHFFFAOYSA-N 0.000 description 2
• NQRHNLPKJODLTJ-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[(3-methoxyphenyl)methyl]amino]acetic acid Chemical compound COC1=CC=CC(CN(CC(O)=O)S(=O)(=O)C=2C=C3C(Cl)=NC=C(Cl)C3=CC=2)=C1 NQRHNLPKJODLTJ-UHFFFAOYSA-N 0.000 description 2
• ZRGAQZDWAZYHTA-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[(4-methoxyphenyl)methyl]amino]acetic acid Chemical compound C1=CC(OC)=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 ZRGAQZDWAZYHTA-UHFFFAOYSA-N 0.000 description 2
• XAGKXNQRPYVLNY-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-methylamino]acetic acid Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)N(CC(O)=O)C)=CC=C21 XAGKXNQRPYVLNY-UHFFFAOYSA-N 0.000 description 2
• SSBJXDPEIXGMJJ-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-2-methylpropanamide Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)NC(C)(C)C(N)=O)=CC=C21 SSBJXDPEIXGMJJ-UHFFFAOYSA-N 0.000 description 2
• CGVSGFNXYGGAHZ-UHFFFAOYSA-N 2-[(3-chlorophenyl)methyl-(1,4-dichloroisoquinolin-7-yl)sulfonylamino]acetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(CC(=O)O)CC1=CC=CC(Cl)=C1 CGVSGFNXYGGAHZ-UHFFFAOYSA-N 0.000 description 2
• LZYBKPISUPUAAF-SBSPUUFOSA-N 2-[4-chloro-7-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]sulfonylisoquinolin-1-yl]guanidine;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCC[C@@H]1CO LZYBKPISUPUAAF-SBSPUUFOSA-N 0.000 description 2
• OPBOLPCIKIWUGT-UHFFFAOYSA-N 2-[4-chloro-7-[[1-(hydroxymethyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(CO)CCCC1 OPBOLPCIKIWUGT-UHFFFAOYSA-N 0.000 description 2
• XPUMANYURZTNDI-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methyl-methylamino]-2-phenylacetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C2C(Cl)=CN=C(N=C(N)N)C2=CC=1CN(C)C(C(O)=O)C1=CC=CC=C1 XPUMANYURZTNDI-UHFFFAOYSA-N 0.000 description 2
• GDPRFZQQBIKJDH-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(cyclohexylmethyl)amino]acetic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1CCCCC1 GDPRFZQQBIKJDH-UHFFFAOYSA-N 0.000 description 2
• YZNIBXPXGCOODS-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-2-ylmethyl)amino]acetic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC=N1 YZNIBXPXGCOODS-UHFFFAOYSA-N 0.000 description 2
• AMGATBXWBRIFHQ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-2-ylmethyl)amino]acetic acid;dihydrochloride Chemical compound Cl.Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC=N1 AMGATBXWBRIFHQ-UHFFFAOYSA-N 0.000 description 2
• HPXCXDMXXAMAJA-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-3-ylmethyl)amino]acetic acid;dihydrochloride Chemical compound Cl.Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CN=C1 HPXCXDMXXAMAJA-UHFFFAOYSA-N 0.000 description 2
• ZTDFFYNFVLEXCF-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(pyridin-4-ylmethyl)amino]acetic acid;dihydrochloride Chemical compound Cl.Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=NC=C1 ZTDFFYNFVLEXCF-UHFFFAOYSA-N 0.000 description 2
• VWLQOCGRPVXLHQ-UTONKHPSSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(1r)-1-phenylethyl]amino]acetic acid;hydrochloride Chemical compound Cl.C1([C@H](N(CC(O)=O)S(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)C)=CC=CC=C1 VWLQOCGRPVXLHQ-UTONKHPSSA-N 0.000 description 2
• VWLQOCGRPVXLHQ-YDALLXLXSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(1s)-1-phenylethyl]amino]acetic acid;hydrochloride Chemical compound Cl.C1([C@@H](N(CC(O)=O)S(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)C)=CC=CC=C1 VWLQOCGRPVXLHQ-YDALLXLXSA-N 0.000 description 2
• JXFSTYPSWCYYEO-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(2-methoxyphenyl)methyl]amino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 JXFSTYPSWCYYEO-UHFFFAOYSA-N 0.000 description 2
• MFLWOIMFSLYVTE-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(2-methylphenyl)methyl]amino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC=CC=C1CN(CC(O)=O)S(=O)(=O)C1=CC=C(C(Cl)=CN=C2N=C(N)N)C2=C1 MFLWOIMFSLYVTE-UHFFFAOYSA-N 0.000 description 2
• JYLJFWCPRHSAFV-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[(3-chlorophenyl)methyl]amino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC(Cl)=C1 JYLJFWCPRHSAFV-UHFFFAOYSA-N 0.000 description 2
• YSILPIWCDPHDRP-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-methylamino]acetic acid Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N(CC(O)=O)C)=CC=C21 YSILPIWCDPHDRP-UHFFFAOYSA-N 0.000 description 2
• IVWAPNVGSPSJEA-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-methylamino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N(CC(O)=O)C)=CC=C21 IVWAPNVGSPSJEA-UHFFFAOYSA-N 0.000 description 2
• BOXJDXJDFRZOOE-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2-methylpropanamide;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NC(C)(C)C(N)=O)=CC=C21 BOXJDXJDFRZOOE-UHFFFAOYSA-N 0.000 description 2
• KZPZBUWGZWWKRZ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-2-cyclopentylacetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1C(=O)NC(C(O)=O)C1CCCC1 KZPZBUWGZWWKRZ-UHFFFAOYSA-N 0.000 description 2
• HHJBMGZABPQWSO-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-3-hydroxypropanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(C(=O)NC(CO)C(O)=O)C=C2C(N=C(N)N)=NC=C(Cl)C2=C1 HHJBMGZABPQWSO-UHFFFAOYSA-N 0.000 description 2
• DFHXYACJRDMJNE-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-3-methylbutanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=CN=C(NC(N)=N)C2=CC(C(=O)NC(C(C)C)C(O)=O)=CC=C21 DFHXYACJRDMJNE-UHFFFAOYSA-N 0.000 description 2
• APWMDKWPHBPGRI-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-3-phenylpropanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(=O)NC(C(O)=O)CC1=CC=CC=C1 APWMDKWPHBPGRI-UHFFFAOYSA-N 0.000 description 2
• AZJSTAJPTHFANN-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]-4-methylpentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=CN=C(NC(N)=N)C2=CC(C(=O)NC(CC(C)C)C(O)=O)=CC=C21 AZJSTAJPTHFANN-UHFFFAOYSA-N 0.000 description 2
• BKFJIRZEVMYGIC-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]acetic acid Chemical compound C1=C(C(=O)NCC(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 BKFJIRZEVMYGIC-UHFFFAOYSA-N 0.000 description 2
• AWTGDYUUCNUVPX-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(C(=O)NCC(O)=O)C=C2C(N=C(N)N)=NC=C(Cl)C2=C1 AWTGDYUUCNUVPX-UHFFFAOYSA-N 0.000 description 2
• MNFCGXPRYMJSQU-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]butanedioic acid Chemical compound C1=C(C(=O)NC(CC(O)=O)C(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 MNFCGXPRYMJSQU-UHFFFAOYSA-N 0.000 description 2
• QEINCTOKPHAHRH-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]butanedioic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(C(=O)NC(CC(O)=O)C(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 QEINCTOKPHAHRH-UHFFFAOYSA-N 0.000 description 2
• JFZBBUPMJXURCH-UHFFFAOYSA-N 2-[benzyl-(1,4-dichloroisoquinolin-7-yl)sulfonylamino]acetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(CC(=O)O)CC1=CC=CC=C1 JFZBBUPMJXURCH-UHFFFAOYSA-N 0.000 description 2
• HKKWVXONIITRLP-UHFFFAOYSA-N 2-[benzyl-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1=CC=CC=C1 HKKWVXONIITRLP-UHFFFAOYSA-N 0.000 description 2
• HZQVDAUIBDEMQZ-UHFFFAOYSA-N 2-[benzyl-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methyl]amino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1CN(CC(O)=O)CC1=CC=CC=C1 HZQVDAUIBDEMQZ-UHFFFAOYSA-N 0.000 description 2
• BIOUKLXWWSNAJT-UHFFFAOYSA-N 2-[carboxymethyl-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]acetic acid;hydrochloride Chemical compound Cl.C1=C(S(=O)(=O)N(CC(O)=O)CC(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 BIOUKLXWWSNAJT-UHFFFAOYSA-N 0.000 description 2
• GOHSKRBVVFCLDO-UHFFFAOYSA-N 2-bromo-2-chloro-2-fluoroacetic acid Chemical compound OC(=O)C(F)(Cl)Br GOHSKRBVVFCLDO-UHFFFAOYSA-N 0.000 description 2
• HYRUDSODWCYZBP-UHFFFAOYSA-N 3-(4-bromophenyl)prop-2-enoyl azide Chemical compound BrC1=CC=C(C=CC(=O)N=[N+]=[N-])C=C1 HYRUDSODWCYZBP-UHFFFAOYSA-N 0.000 description 2
• YLABICHHIYWLQM-UHFFFAOYSA-N 3-(4-bromophenyl)prop-2-enoyl chloride Chemical compound ClC(=O)C=CC1=CC=C(Br)C=C1 YLABICHHIYWLQM-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• MCWFZUYARBFPMQ-UHFFFAOYSA-N 4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]oxane-4-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCOCC1 MCWFZUYARBFPMQ-UHFFFAOYSA-N 0.000 description 2
• BKJUCAQGGKWKRQ-UHFFFAOYSA-N 4-chloro-1-oxo-2h-isoquinoline-7-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2C(Cl)=CNC(=O)C2=C1 BKJUCAQGGKWKRQ-UHFFFAOYSA-N 0.000 description 2
• MVWIXKFNHOXLBU-UHFFFAOYSA-N 4-chloro-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(Cl)=CNC(=O)C2=C1 MVWIXKFNHOXLBU-UHFFFAOYSA-N 0.000 description 2
• CRMZCAZKRFJYRV-UHFFFAOYSA-N 5-(4-amino-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)-6-(5-chlorothiophen-2-yl)-1,3-dimethyl-7h-pyrrolo[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C)C(N)=C1C1=C(C=2SC(Cl)=CC=2)NC2=C1C(=O)N(C)C(=O)N2C CRMZCAZKRFJYRV-UHFFFAOYSA-N 0.000 description 2
• YRWRDWYNNLDIAJ-UHFFFAOYSA-N 7-bromo-4-chloro-2h-isoquinolin-1-one Chemical compound BrC1=CC=C2C(Cl)=CNC(=O)C2=C1 YRWRDWYNNLDIAJ-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• UERLULLEBSMPOQ-JOCQHMNTSA-N C1C[C@@H](C(=O)OC(C)(C)C)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 Chemical compound C1C[C@@H](C(=O)OC(C)(C)C)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 UERLULLEBSMPOQ-JOCQHMNTSA-N 0.000 description 2
• DQYOKLRDMJNFMK-HAQNSBGRSA-N C1C[C@@H](C(=O)OCC)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 Chemical compound C1C[C@@H](C(=O)OCC)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 DQYOKLRDMJNFMK-HAQNSBGRSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 2
• NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• PPXYIKWUERSBMJ-UHFFFAOYSA-N FC(C(=O)O)(F)F.ClC1=CN=C(C2=CC(=CC=C12)C(=O)NC(C1=CC=CC=C1)C(=O)O)NC(=N)N Chemical compound FC(C(=O)O)(F)F.ClC1=CN=C(C2=CC(=CC=C12)C(=O)NC(C1=CC=CC=C1)C(=O)O)NC(=N)N PPXYIKWUERSBMJ-UHFFFAOYSA-N 0.000 description 2
• PPXYIKWUERSBMJ-XFULWGLBSA-N FC(C(=O)O)(F)F.ClC1=CN=C(C2=CC(=CC=C12)C(=O)N[C@H](C1=CC=CC=C1)C(=O)O)NC(=N)N Chemical compound FC(C(=O)O)(F)F.ClC1=CN=C(C2=CC(=CC=C12)C(=O)N[C@H](C1=CC=CC=C1)C(=O)O)NC(=N)N PPXYIKWUERSBMJ-XFULWGLBSA-N 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
• 206010029113 Neovascularisation Diseases 0.000 description 2
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
• 229910019213 POCl3 Inorganic materials 0.000 description 2
• 102000013566 Plasminogen Human genes 0.000 description 2
• 108010051456 Plasminogen Proteins 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• 229910006024 SO2Cl2 Inorganic materials 0.000 description 2
• 206010040943 Skin Ulcer Diseases 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
• NYIQMVLYUBBRPN-SECBINFHSA-N [(2r)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpyrrolidin-2-yl]methanol Chemical compound OC[C@H]1CCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 NYIQMVLYUBBRPN-SECBINFHSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 229960000686 benzalkonium chloride Drugs 0.000 description 2
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
• 238000005251 capillar electrophoresis Methods 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000002843 carboxylic acid group Chemical group 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
• ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 2
• ZNKNSUYQWBHTFD-MRXNPFEDSA-N ditert-butyl (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]butanedioate Chemical compound ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N[C@H](CC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=CC=C21 ZNKNSUYQWBHTFD-MRXNPFEDSA-N 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 238000010931 ester hydrolysis Methods 0.000 description 2
• OKKPNBJEAZBKDF-UHFFFAOYSA-N ethyl 1,4-dichloroisoquinoline-7-carboxylate Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)OCC)=CC=C21 OKKPNBJEAZBKDF-UHFFFAOYSA-N 0.000 description 2
• GSFIBGRNPWNGME-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(=O)OCC)CCCC1 GSFIBGRNPWNGME-UHFFFAOYSA-N 0.000 description 2
• QXYFTOZQCJKISW-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylate;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(=O)OCC)CCCC1 QXYFTOZQCJKISW-UHFFFAOYSA-N 0.000 description 2
• KEPSIMOVRWXUOT-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(oxan-2-yloxy)ethyl]amino]cyclopentane-1-carboxylate Chemical compound C1CCCOC1OCCN(S(=O)(=O)C=1C=C2C(NC(N)=N)=NC=C(Cl)C2=CC=1)C1(C(=O)OCC)CCCC1 KEPSIMOVRWXUOT-UHFFFAOYSA-N 0.000 description 2
• QWYQMCPQTSVEAQ-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CC(=O)OC(C)(C)C)C1(C(=O)OCC)CCCC1 QWYQMCPQTSVEAQ-UHFFFAOYSA-N 0.000 description 2
• UDEIQVPDPNKDCJ-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclobutane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OCC)CCC1 UDEIQVPDPNKDCJ-UHFFFAOYSA-N 0.000 description 2
• ZLWOYEWRYSUZPY-UHFFFAOYSA-N ethyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OCC)CCCC1 ZLWOYEWRYSUZPY-UHFFFAOYSA-N 0.000 description 2
• YGAYWFFKRVMVBL-UHFFFAOYSA-N ethyl 1-aminocyclobutane-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1(N)CCC1 YGAYWFFKRVMVBL-UHFFFAOYSA-N 0.000 description 2
• NLLGKNYQDQBMFW-UHFFFAOYSA-N ethyl 1-aminocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1(N)CCCC1 NLLGKNYQDQBMFW-UHFFFAOYSA-N 0.000 description 2
• KZEMDYLFNDBMTG-UHFFFAOYSA-N ethyl 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2,2-dimethylpropanoate;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NCC(C)(C)C(=O)OCC)=CC=C21 KZEMDYLFNDBMTG-UHFFFAOYSA-N 0.000 description 2
• WASRJUXSLHUONH-UHFFFAOYSA-N ethyl 4-aminocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(N)CC1 WASRJUXSLHUONH-UHFFFAOYSA-N 0.000 description 2
• QAKKFOLTBGZECT-UHFFFAOYSA-N ethyl 4-chloro-1-oxo-2h-isoquinoline-7-carboxylate Chemical compound ClC1=CNC(=O)C2=CC(C(=O)OCC)=CC=C21 QAKKFOLTBGZECT-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 239000003527 fibrinolytic agent Substances 0.000 description 2
• 230000003480 fibrinolytic effect Effects 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 230000035876 healing Effects 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 239000000017 hydrogel Substances 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 239000002198 insoluble material Substances 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• BJUJDDATZZBTGL-SSDOTTSWSA-N methyl (2r)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]propanoate Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)N[C@H](C)C(=O)OC)=CC=C21 BJUJDDATZZBTGL-SSDOTTSWSA-N 0.000 description 2
• JTUMJKKWQZYPPL-UHFFFAOYSA-N methyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]cyclohexane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCCCC1 JTUMJKKWQZYPPL-UHFFFAOYSA-N 0.000 description 2
• WMTHWSWQCXSBOV-UHFFFAOYSA-N methyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1CNC1(C(=O)OC)CCCC1 WMTHWSWQCXSBOV-UHFFFAOYSA-N 0.000 description 2
• MDQKGIOLJDBGLT-UHFFFAOYSA-N methyl 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCCCC1 MDQKGIOLJDBGLT-UHFFFAOYSA-N 0.000 description 2
• JHXBMPDRUXACBV-UHFFFAOYSA-N methyl 3-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(NS(=O)(=O)C=2C=C3C(Cl)=NC=C(Cl)C3=CC=2)=C1 JHXBMPDRUXACBV-UHFFFAOYSA-N 0.000 description 2
• PHCLQRSGYBYJAJ-UHFFFAOYSA-N methyl 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(NS(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)=C1 PHCLQRSGYBYJAJ-UHFFFAOYSA-N 0.000 description 2
• MMQNBCUIOPBHRQ-UHFFFAOYSA-N methyl 4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-1-methylpiperidine-4-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCN(C)CC1 MMQNBCUIOPBHRQ-UHFFFAOYSA-N 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 2
• 150000002825 nitriles Chemical group 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 230000006340 racemization Effects 0.000 description 2
• 230000008707 rearrangement Effects 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• TZHVYFBSLOMRCU-YFKPBYRVSA-N tert-butyl (2s)-2-aminopropanoate Chemical compound C[C@H](N)C(=O)OC(C)(C)C TZHVYFBSLOMRCU-YFKPBYRVSA-N 0.000 description 2
• UURAHTSUPDIUNL-UHFFFAOYSA-N tert-butyl 2-(benzylamino)acetate Chemical compound CC(C)(C)OC(=O)CNCC1=CC=CC=C1 UURAHTSUPDIUNL-UHFFFAOYSA-N 0.000 description 2
• KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 2
• DRGCBGCMYGTVIB-UHFFFAOYSA-N tert-butyl 2-nitrobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1[N+]([O-])=O DRGCBGCMYGTVIB-UHFFFAOYSA-N 0.000 description 2
• XOBTVGBENYKVOJ-UHFFFAOYSA-N tert-butyl 3-[(1,4-dichloroisoquinoline-7-carbonyl)amino]propanoate Chemical compound ClC1=CN=C(Cl)C2=CC(C(=O)NCCC(=O)OC(C)(C)C)=CC=C21 XOBTVGBENYKVOJ-UHFFFAOYSA-N 0.000 description 2
• ZJXHVYSDMUKUCA-UHFFFAOYSA-N tert-butyl 3-aminopropanoate Chemical compound CC(C)(C)OC(=O)CCN ZJXHVYSDMUKUCA-UHFFFAOYSA-N 0.000 description 2
• SFFFYEGVQDWTNQ-UHFFFAOYSA-N tert-butyl 3-nitrobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC([N+]([O-])=O)=C1 SFFFYEGVQDWTNQ-UHFFFAOYSA-N 0.000 description 2
• XDTZRQLZSNTGSM-UHFFFAOYSA-N tert-butyl 4-aminocyclohexane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCC(N)CC1 XDTZRQLZSNTGSM-UHFFFAOYSA-N 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 150000003585 thioureas Chemical class 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 239000004034 viscosity adjusting agent Substances 0.000 description 2
• MYVWJCDGRUONGO-UHFFFAOYSA-N (1-aminocyclopentyl)-(4-methylpiperazin-1-yl)methanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1(N)CCCC1 MYVWJCDGRUONGO-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 1
• CJAAPVQEZPAQNI-UHFFFAOYSA-N (2-methylphenyl)methanamine Chemical compound CC1=CC=CC=C1CN CJAAPVQEZPAQNI-UHFFFAOYSA-N 0.000 description 1
• CHXLQXMSRZELLF-MRXNPFEDSA-N (2r)-1-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-n-[2-(dimethylamino)ethyl]pyrrolidine-2-carboxamide Chemical compound CN(C)CCNC(=O)[C@H]1CCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 CHXLQXMSRZELLF-MRXNPFEDSA-N 0.000 description 1
• PYAPIUGPYJOQFC-YDALLXLXSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-3,3-dimethylbutanoic acid;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N[C@H](C(C)(C)C)C(O)=O)=CC=C21 PYAPIUGPYJOQFC-YDALLXLXSA-N 0.000 description 1
• QDDOVGGTVYFMDE-UTONKHPSSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-3-methylbutanoic acid;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)N[C@H](C(C)C)C(O)=O)=CC=C21 QDDOVGGTVYFMDE-UTONKHPSSA-N 0.000 description 1
• VTNQDOOHJOBQKC-HNCPQSOCSA-N (2r)-2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]butanedioic acid;hydrochloride Chemical compound Cl.C1=C(S(=O)(=O)N[C@H](CC(O)=O)C(O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 VTNQDOOHJOBQKC-HNCPQSOCSA-N 0.000 description 1
• NPDBDJFLKKQMCM-BYPYZUCNSA-N (2r)-2-azaniumyl-3,3-dimethylbutanoate Chemical compound CC(C)(C)[C@@H]([NH3+])C([O-])=O NPDBDJFLKKQMCM-BYPYZUCNSA-N 0.000 description 1
• MPQOREHNRHHMOB-LBPRGKRZSA-N (2s)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 MPQOREHNRHHMOB-LBPRGKRZSA-N 0.000 description 1
• RLIHXKPTGKETCC-QMMMGPOBSA-N (2s)-2-(benzylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NCC1=CC=CC=C1 RLIHXKPTGKETCC-QMMMGPOBSA-N 0.000 description 1
• DWHMPBALQYTJFJ-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CC(O)=O DWHMPBALQYTJFJ-DKWTVANSSA-N 0.000 description 1
• GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 description 1
• SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 description 1
• CPDDDTNAMBSPRN-ZZXKWVIFSA-N (e)-3-(4-bromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(Br)C=C1 CPDDDTNAMBSPRN-ZZXKWVIFSA-N 0.000 description 1
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
• ZKOCWDCPANZRPS-UHFFFAOYSA-N 1,4,7-trichloroisoquinoline Chemical compound ClC1=CN=C(Cl)C2=CC(Cl)=CC=C21 ZKOCWDCPANZRPS-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• BXCBUWKTXLWPSB-UHFFFAOYSA-N 1-(chloromethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CCl BXCBUWKTXLWPSB-UHFFFAOYSA-N 0.000 description 1
• FVTVMQPGKVHSEY-UHFFFAOYSA-N 1-AMINOCYCLOBUTANE CARBOXYLIC ACID Chemical compound OC(=O)C1(N)CCC1 FVTVMQPGKVHSEY-UHFFFAOYSA-N 0.000 description 1
• BHJHBXRXPODWGU-UHFFFAOYSA-N 1-[3-(1-aminoisoquinolin-6-yl)-1-oxo-1-piperidin-1-ylpropan-2-yl]-3-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]urea Chemical compound CC=1C=2CCC(C)(C)OC=2C(C)=C(C)C=1S(=O)(=O)NNC(=O)NC(CC=1C=C2C=CN=C(N)C2=CC=1)C(=O)N1CCCCC1 BHJHBXRXPODWGU-UHFFFAOYSA-N 0.000 description 1
• CIBSVTIGWIBIPC-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]methylamino]cyclopentane-1-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1CNC1(C(O)=O)CCCC1 CIBSVTIGWIBIPC-UHFFFAOYSA-N 0.000 description 1
• PZIPABXTGFUIRH-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-[2-(dimethylamino)ethyl]amino]-n-(2-hydroxyethyl)-n-methylcyclopentane-1-carboxamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(=O)N(C)CCO)CCCC1 PZIPABXTGFUIRH-UHFFFAOYSA-N 0.000 description 1
• LDQBNBQEPZPATR-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-[2-(dimethylamino)ethyl]cyclopentane-1-carboxamide Chemical compound C=1C=C2C(Cl)=CN=C(N=C(N)N)C2=CC=1S(=O)(=O)NC1(C(=O)NCCN(C)C)CCCC1 LDQBNBQEPZPATR-UHFFFAOYSA-N 0.000 description 1
• TWVUMWXBQZRDNJ-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-n-methyl-n-[2-(methylamino)ethyl]cyclopentane-1-carboxamide;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)N(C)CCNC)CCCC1 TWVUMWXBQZRDNJ-UHFFFAOYSA-N 0.000 description 1
• FXIJMQHQADSODA-UHFFFAOYSA-N 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclohexane-1-carboxylic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(O)=O)CCCCC1 FXIJMQHQADSODA-UHFFFAOYSA-N 0.000 description 1
• NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 description 1
• JZWDLUGQTRKBNA-UHFFFAOYSA-N 1-benzothiophene-2-carboximidamide Chemical class C1=CC=C2SC(C(=N)N)=CC2=C1 JZWDLUGQTRKBNA-UHFFFAOYSA-N 0.000 description 1
• DDGRAFHHXYIQQR-UHFFFAOYSA-N 1-chloro-3-(chloromethyl)benzene Chemical compound ClCC1=CC=CC(Cl)=C1 DDGRAFHHXYIQQR-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
• HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
• XDDXQEWQVDNIND-UHFFFAOYSA-N 2-[(1,4-dichloroisoquinolin-7-yl)methyl-methylamino]-2-phenylacetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1CN(C)C(C(O)=O)C1=CC=CC=C1 XDDXQEWQVDNIND-UHFFFAOYSA-N 0.000 description 1
• UGUXSVYJXMQGLC-UHFFFAOYSA-N 2-[4-chloro-7-[[1-(4-methylpiperazine-1-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1(NS(=O)(=O)C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)CCCC1 UGUXSVYJXMQGLC-UHFFFAOYSA-N 0.000 description 1
• TWTODTWQWNOGTP-UHFFFAOYSA-N 2-[4-chloro-7-[[1-(morpholine-4-carbonyl)cyclopentyl]sulfamoyl]isoquinolin-1-yl]guanidine;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1(C(=O)N2CCOCC2)CCCC1 TWTODTWQWNOGTP-UHFFFAOYSA-N 0.000 description 1
• BLGALJLRMMYDNI-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(cyclopentylmethyl)amino]acetic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N(CC(O)=O)CC1CCCC1 BLGALJLRMMYDNI-UHFFFAOYSA-N 0.000 description 1
• IUBFETAFRGVODB-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2-methylpropanoic acid;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NC(C)(C)C(O)=O)=CC=C21 IUBFETAFRGVODB-UHFFFAOYSA-N 0.000 description 1
• MCOBQEUHHKLLMS-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]acetic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(S(=O)(=O)NCC(O)=O)C=C2C(N=C(N)N)=NC=C(Cl)C2=C1 MCOBQEUHHKLLMS-UHFFFAOYSA-N 0.000 description 1
• SRDUSZRNFSZLPK-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoic acid Chemical compound C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1=CC=CC=C1C(O)=O SRDUSZRNFSZLPK-UHFFFAOYSA-N 0.000 description 1
• DWNTUNKHCYBTHJ-UHFFFAOYSA-N 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoic acid;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1=CC=CC=C1C(O)=O DWNTUNKHCYBTHJ-UHFFFAOYSA-N 0.000 description 1
• RNMYIBXSRMOSAB-UHFFFAOYSA-N 2-[benzyl-(1,4-dichloroisoquinoline-7-carbonyl)amino]acetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1C(=O)N(CC(=O)O)CC1=CC=CC=C1 RNMYIBXSRMOSAB-UHFFFAOYSA-N 0.000 description 1
• PVSMGMIQTFYTLG-UHFFFAOYSA-N 2-[benzyl-[(1,4-dichloroisoquinolin-7-yl)methyl]amino]acetic acid Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1CN(CC(=O)O)CC1=CC=CC=C1 PVSMGMIQTFYTLG-UHFFFAOYSA-N 0.000 description 1
• RZHLHZRAKGZWTD-UHFFFAOYSA-N 2-[benzyl-[4-chloro-1-(diaminomethylideneamino)isoquinoline-7-carbonyl]amino]acetic acid Chemical compound C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1C(=O)N(CC(O)=O)CC1=CC=CC=C1 RZHLHZRAKGZWTD-UHFFFAOYSA-N 0.000 description 1
• ZIOBGZDFMKCKGZ-UHFFFAOYSA-N 2-amino-2-methylpropanamide Chemical compound CC(C)(N)C(N)=O ZIOBGZDFMKCKGZ-UHFFFAOYSA-N 0.000 description 1
• YSWCBAKPAOEYGF-UHFFFAOYSA-N 2-aminoacetic acid;2,2,2-trifluoroacetic acid Chemical compound NCC(O)=O.OC(=O)C(F)(F)F YSWCBAKPAOEYGF-UHFFFAOYSA-N 0.000 description 1
• WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical class NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 description 1
• SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical class CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
• UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
• UOHBWYOFMZZGFD-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-2,2-dimethylpropanoic acid;hydrochloride Chemical compound Cl.ClC1=CN=C(NC(N)=N)C2=CC(S(=O)(=O)NCC(C)(C)C(O)=O)=CC=C21 UOHBWYOFMZZGFD-UHFFFAOYSA-N 0.000 description 1
• RDKCZWQZPLEOOK-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2N=C(N)N)C2=C1 RDKCZWQZPLEOOK-UHFFFAOYSA-N 0.000 description 1
• CQXWCXFZBGJXOD-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-4-methoxybenzoic acid;hydrochloride Chemical compound Cl.COC1=CC=C(C(O)=O)C=C1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 CQXWCXFZBGJXOD-UHFFFAOYSA-N 0.000 description 1
• OGVTZTLGWGTMLF-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoic acid Chemical compound C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1=CC=CC(C(O)=O)=C1 OGVTZTLGWGTMLF-UHFFFAOYSA-N 0.000 description 1
• GKMIPQRXZFAJAA-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2C(N=C(N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1=CC=CC(C(O)=O)=C1 GKMIPQRXZFAJAA-UHFFFAOYSA-N 0.000 description 1
• IIJSNBWEYVORPD-UHFFFAOYSA-N 3-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]propanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(S(=O)(=O)NCCC(O)=O)C=C2C(N=C(N)N)=NC=C(Cl)C2=C1 IIJSNBWEYVORPD-UHFFFAOYSA-N 0.000 description 1
• AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 description 1
• ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 1
• YFQCWRFRSGFFTC-UHFFFAOYSA-N 4-(dichloromethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C(Cl)Cl)N=C1C1=CC=CC=C1 YFQCWRFRSGFFTC-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 1
• MNVXOHFGWKIQNL-UHFFFAOYSA-N 4-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]-1-methylpiperidine-4-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C)CCC1(C(O)=O)NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 MNVXOHFGWKIQNL-UHFFFAOYSA-N 0.000 description 1
• DPDPQQHHTHKSRN-UHFFFAOYSA-N 4-aminooxane-4-carboxylic acid Chemical compound OC(=O)C1(N)CCOCC1 DPDPQQHHTHKSRN-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• DSOKREQUHLPVFR-UHFFFAOYSA-N 7-bromo-2h-isoquinolin-1-one Chemical compound C1=CNC(=O)C2=CC(Br)=CC=C21 DSOKREQUHLPVFR-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• QMYNQWVHQFVSKA-MGCOHNPYSA-N C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N[C@H]1CC[C@H](C(O)=O)CC1 QMYNQWVHQFVSKA-MGCOHNPYSA-N 0.000 description 1
• JXCLONSFCOTIJC-HAQNSBGRSA-N C1C[C@@H](C(=O)OCC)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 Chemical compound C1C[C@@H](C(=O)OCC)CC[C@@H]1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 JXCLONSFCOTIJC-HAQNSBGRSA-N 0.000 description 1
• QWEWPBRDYZVGBR-WCTZXXKLSA-N CC[C@@H]1C[C@@H](O)[C@H](O)[C@@H](CO)N1 Chemical compound CC[C@@H]1C[C@@H](O)[C@H](O)[C@@H](CO)N1 QWEWPBRDYZVGBR-WCTZXXKLSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 102000004173 Cathepsin G Human genes 0.000 description 1
• 108090000617 Cathepsin G Proteins 0.000 description 1
• BEMBINBUNAFRRS-AWLKUTLJSA-N Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N[C@H]1CC[C@H](C(O)=O)CC1 BEMBINBUNAFRRS-AWLKUTLJSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
• HVVNJUAVDAZWCB-RXMQYKEDSA-N D-prolinol Chemical compound OC[C@H]1CCCN1 HVVNJUAVDAZWCB-RXMQYKEDSA-N 0.000 description 1
• 206010011985 Decubitus ulcer Diseases 0.000 description 1
• 206010056340 Diabetic ulcer Diseases 0.000 description 1
• 108010073385 Fibrin Proteins 0.000 description 1
• 102000009123 Fibrin Human genes 0.000 description 1
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• IILDQBBNCMYHPD-UHFFFAOYSA-N Hydron;pyridin-3-yl 4-chlorobenzoate;chloride Chemical compound Cl.C1=CC(Cl)=CC=C1C(=O)OC1=CC=CN=C1 IILDQBBNCMYHPD-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 102000016387 Pancreatic elastase Human genes 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
• 102100039419 Plasminogen activator inhibitor 2 Human genes 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 108010067787 Proteoglycans Proteins 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229910000831 Steel Inorganic materials 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 208000000558 Varicose Ulcer Diseases 0.000 description 1
• FDMCEXDXULPJPG-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxy]-1-oxo-3-phenylpropan-2-yl]azanium;chloride Chemical compound Cl.CC(C)(C)OC(=O)C(N)CC1=CC=CC=C1 FDMCEXDXULPJPG-UHFFFAOYSA-N 0.000 description 1
• RFUWRXIYTQGFGA-UHFFFAOYSA-N [4-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopentan-2-yl]azanium;chloride Chemical compound Cl.CC(C)CC(N)C(=O)OC(C)(C)C RFUWRXIYTQGFGA-UHFFFAOYSA-N 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 238000007171 acid catalysis Methods 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• KQNPFQTWMSNSAP-UHFFFAOYSA-N alpha-isobutyric acid Natural products CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical compound OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 description 1
• 239000004411 aluminium Substances 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• KRRGYDUZFDKPIB-UHFFFAOYSA-N amino 4-methoxybenzoate Chemical compound COC1=CC=C(C(=O)ON)C=C1 KRRGYDUZFDKPIB-UHFFFAOYSA-N 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• AXNJKYLFCKEIHI-UHFFFAOYSA-N amino(cyclopentyl)methanol Chemical compound NC(O)C1CCCC1 AXNJKYLFCKEIHI-UHFFFAOYSA-N 0.000 description 1
• AOPRFYAPABFRPU-UHFFFAOYSA-N amino(imino)methanesulfonic acid Chemical compound NC(=N)S(O)(=O)=O AOPRFYAPABFRPU-UHFFFAOYSA-N 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000001567 anti-fibrinolytic effect Effects 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 235000019568 aromas Nutrition 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
• CGAMNSKIHXUDMK-UHFFFAOYSA-N benzyl n-[methylsulfanyl(phenylmethoxycarbonylamino)methylidene]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N=C(SC)NC(=O)OCC1=CC=CC=C1 CGAMNSKIHXUDMK-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000001273 butane Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000012822 chemical development Methods 0.000 description 1
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
• 108010074800 chromozym PL Proteins 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002485 combustion reaction Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 239000002178 crystalline material Substances 0.000 description 1
• 150000001925 cycloalkenes Chemical group 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
• 125000000950 dibromo group Chemical group Br* 0.000 description 1
• USPLDBATMHXKKD-UHFFFAOYSA-N dichloromethane;pentane Chemical compound ClCCl.CCCCC USPLDBATMHXKKD-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• FNQUQCZVFWNFEE-MRXNPFEDSA-N ditert-butyl (2r)-2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]butanedioate Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)N[C@H](CC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=CC=C21 FNQUQCZVFWNFEE-MRXNPFEDSA-N 0.000 description 1
• FNCGNFXGKHSMKJ-MRVPVSSYSA-N ditert-butyl (2r)-2-aminobutanedioate Chemical compound CC(C)(C)OC(=O)C[C@@H](N)C(=O)OC(C)(C)C FNCGNFXGKHSMKJ-MRVPVSSYSA-N 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000010410 dusting Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
• XMQSOBPCWYVZSW-WLYNEOFISA-N ethyl (1r,2s)-2-aminocyclohexane-1-carboxylate;hydron;chloride Chemical compound Cl.CCOC(=O)[C@@H]1CCCC[C@@H]1N XMQSOBPCWYVZSW-WLYNEOFISA-N 0.000 description 1
• BBUDXRABCMOOQD-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[2-(dimethylamino)ethyl]amino]cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(CCN(C)C)C1(C(=O)OCC)CCCC1 BBUDXRABCMOOQD-UHFFFAOYSA-N 0.000 description 1
• BWYPVQZAFLNQMK-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-[2-(oxan-2-yloxy)ethyl]amino]cyclopentane-1-carboxylate Chemical compound C1CCCOC1OCCN(S(=O)(=O)C=1C=C2C(Cl)=NC=C(Cl)C2=CC=1)C1(C(=O)OCC)CCCC1 BWYPVQZAFLNQMK-UHFFFAOYSA-N 0.000 description 1
• OSRRNIODAMHKTI-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonyl-methylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)N(C)C1(C(=O)OCC)CCCC1 OSRRNIODAMHKTI-UHFFFAOYSA-N 0.000 description 1
• HBQARTMVOKXCLT-UHFFFAOYSA-N ethyl 1-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]cyclobutane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(C(=O)OCC)CCC1 HBQARTMVOKXCLT-UHFFFAOYSA-N 0.000 description 1
• ZGZJPUJUIYKVCA-UHFFFAOYSA-N ethyl 1-[[1,4-dichloro-1-(diaminomethylideneamino)-2h-isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CNC(Cl)(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)OCC)CCCC1 ZGZJPUJUIYKVCA-UHFFFAOYSA-N 0.000 description 1
• SOJJLUOGEIHGRZ-UHFFFAOYSA-N ethyl 1-aminocyclobutane-1-carboxylate Chemical compound CCOC(=O)C1(N)CCC1 SOJJLUOGEIHGRZ-UHFFFAOYSA-N 0.000 description 1
• NCSBNXBVEDFAHP-UHFFFAOYSA-N ethyl 2-[[3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarbonyl]amino]-4-methyl-5-(phenylcarbamoyl)thiophene-3-carboxylate Chemical compound CCOC(=O)C=1C(C)=C(C(=O)NC=2C=CC=CC=2)SC=1NC(=O)C1C(C=C(Cl)Cl)C1(C)C NCSBNXBVEDFAHP-UHFFFAOYSA-N 0.000 description 1
• FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
• 239000002360 explosive Substances 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 229950003499 fibrin Drugs 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 230000004992 fission Effects 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 150000002357 guanidines Chemical class 0.000 description 1
• 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 125000001145 hydrido group Chemical group *[H] 0.000 description 1
• 239000000416 hydrocolloid Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 1
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
• MIGRFORREVIOBF-UHFFFAOYSA-N isoquinoline-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=NC=CC2=C1 MIGRFORREVIOBF-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 238000006138 lithiation reaction Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 229960002523 mercuric chloride Drugs 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• DWKPPFQULDPWHX-GSVOUGTGSA-N methyl (2r)-2-aminopropanoate Chemical compound COC(=O)[C@@H](C)N DWKPPFQULDPWHX-GSVOUGTGSA-N 0.000 description 1
• IVBIJYKIVLHYGH-UHFFFAOYSA-N methyl 1-[(1,4-dichloroisoquinolin-7-yl)methylamino]cyclopentane-1-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1CNC1(C(=O)OC)CCCC1 IVBIJYKIVLHYGH-UHFFFAOYSA-N 0.000 description 1
• OVVPFKJIPAJBLY-UHFFFAOYSA-N methyl 2-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-2-methylpropanoate Chemical compound ClC1=CN=C(Cl)C2=CC(S(=O)(=O)NC(C)(C)C(=O)OC)=CC=C21 OVVPFKJIPAJBLY-UHFFFAOYSA-N 0.000 description 1
• HMZHEECHJWHZJX-UHFFFAOYSA-N methyl 2-amino-2-methylpropanoate Chemical compound COC(=O)C(C)(C)N HMZHEECHJWHZJX-UHFFFAOYSA-N 0.000 description 1
• QVDWKLDUBSJEOG-UHFFFAOYSA-N methyl 3-amino-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(N)=C1 QVDWKLDUBSJEOG-UHFFFAOYSA-N 0.000 description 1
• KJPRUWPBWYKZGX-UHFFFAOYSA-N methyl 4-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]-1-methylpiperidine-4-carboxylate Chemical compound C=1C=C2C(Cl)=CN=C(Cl)C2=CC=1S(=O)(=O)NC1(C(=O)OC)CCN(C)CC1 KJPRUWPBWYKZGX-UHFFFAOYSA-N 0.000 description 1
• GLIKYKRDYKKEBJ-UHFFFAOYSA-N methyl n'-nitrocarbamimidate Chemical compound CO\C(N)=N/[N+]([O-])=O GLIKYKRDYKKEBJ-UHFFFAOYSA-N 0.000 description 1
• FLZZNZJENFNFOJ-UHFFFAOYSA-N methyl n'-nitrocarbamimidothioate Chemical compound CSC(N)=N[N+]([O-])=O FLZZNZJENFNFOJ-UHFFFAOYSA-N 0.000 description 1
• OACFPIYXXBEUPI-UHFFFAOYSA-N methylsulfanyl carbamimidothioate Chemical compound CSSC(N)=N OACFPIYXXBEUPI-UHFFFAOYSA-N 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
• XLMGLSNJRPCITN-UHFFFAOYSA-N n-(2-aminoethyl)-1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C(Cl)=CN=C(NC(N)=N)C2=CC=1S(=O)(=O)NC1(C(=O)NCCN)CCCC1 XLMGLSNJRPCITN-UHFFFAOYSA-N 0.000 description 1
• PEHDMKYTTRTXSH-UHFFFAOYSA-N n-[6-amino-1-(4-nitroanilino)-1-oxohexan-2-yl]-1-[2-[(4-methylphenyl)sulfonylamino]acetyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCC(=O)N1C(C(=O)NC(CCCCN)C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)CCC1 PEHDMKYTTRTXSH-UHFFFAOYSA-N 0.000 description 1
• CMRGKYASWFPKOB-UHFFFAOYSA-N n-[7-(4-chlorophenyl)-5-oxo-6,7-dihydro-1h-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]-4-methoxybenzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC1=NC2=NC(=O)CC(C=3C=CC(Cl)=CC=3)N2N1 CMRGKYASWFPKOB-UHFFFAOYSA-N 0.000 description 1
• IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
• 229910000105 potassium hydride Inorganic materials 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical compound NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 150000003378 silver Chemical class 0.000 description 1
• 239000010802 sludge Substances 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 229960002668 sodium chloride Drugs 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
• 238000006277 sulfonation reaction Methods 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• DWKALJMROLTJPM-RJUBDTSPSA-N tert-butyl (1r,2s)-2-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H]1CCCC[C@@H]1N DWKALJMROLTJPM-RJUBDTSPSA-N 0.000 description 1
• VNLZBZBMFYNBFI-MRXNPFEDSA-N tert-butyl (2r)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpiperidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@H]1CCCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 VNLZBZBMFYNBFI-MRXNPFEDSA-N 0.000 description 1
• RJBVJBGFJIHJSZ-SSDOTTSWSA-N tert-butyl (2r)-2-amino-3-methylbutanoate Chemical compound CC(C)[C@@H](N)C(=O)OC(C)(C)C RJBVJBGFJIHJSZ-SSDOTTSWSA-N 0.000 description 1
• IUUYANMOEMBTBV-OGFXRTJISA-N tert-butyl (2r)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@H]1CCCN1 IUUYANMOEMBTBV-OGFXRTJISA-N 0.000 description 1
• NNPRSJWMOALALA-HNNXBMFYSA-N tert-butyl (2s)-1-(1,4-dichloroisoquinolin-7-yl)sulfonylpyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2Cl)C2=C1 NNPRSJWMOALALA-HNNXBMFYSA-N 0.000 description 1
• ZACSMTDYVYATGT-NSHDSACASA-N tert-butyl (2s)-2-(benzylamino)propanoate Chemical compound CC(C)(C)OC(=O)[C@H](C)NCC1=CC=CC=C1 ZACSMTDYVYATGT-NSHDSACASA-N 0.000 description 1
• RJBVJBGFJIHJSZ-ZETCQYMHSA-N tert-butyl (2s)-2-amino-3-methylbutanoate Chemical compound CC(C)[C@H](N)C(=O)OC(C)(C)C RJBVJBGFJIHJSZ-ZETCQYMHSA-N 0.000 description 1
• QOISWWBTZMFUEL-NSHDSACASA-N tert-butyl (2s)-2-amino-3-phenylpropanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)CC1=CC=CC=C1 QOISWWBTZMFUEL-NSHDSACASA-N 0.000 description 1
• IUUYANMOEMBTBV-FJXQXJEOSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate;hydron;chloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H]1CCCN1 IUUYANMOEMBTBV-FJXQXJEOSA-N 0.000 description 1
• UPIWJJPDQGQPNO-UHFFFAOYSA-N tert-butyl 2-(benzylamino)acetate;hydrochloride Chemical compound [Cl-].CC(C)(C)OC(=O)C[NH2+]CC1=CC=CC=C1 UPIWJJPDQGQPNO-UHFFFAOYSA-N 0.000 description 1
• RNLQHMIDSCYLAK-UHFFFAOYSA-N tert-butyl 2-(methylamino)acetate;hydron;chloride Chemical compound Cl.CNCC(=O)OC(C)(C)C RNLQHMIDSCYLAK-UHFFFAOYSA-N 0.000 description 1
• CCUFGLFAWWXSKW-UHFFFAOYSA-N tert-butyl 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1NS(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 CCUFGLFAWWXSKW-UHFFFAOYSA-N 0.000 description 1
• RDWZQVGVBTYCBD-UHFFFAOYSA-N tert-butyl 2-amino-3-[(2-methylpropan-2-yl)oxy]propanoate;hydrochloride Chemical compound Cl.CC(C)(C)OCC(N)C(=O)OC(C)(C)C RDWZQVGVBTYCBD-UHFFFAOYSA-N 0.000 description 1
• AUIVQIHTTVPKFS-UHFFFAOYSA-N tert-butyl 2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.CC(C)C(N)C(=O)OC(C)(C)C AUIVQIHTTVPKFS-UHFFFAOYSA-N 0.000 description 1
• YBTDADHCDXWFLF-UHFFFAOYSA-N tert-butyl 3-[(1,4-dichloroisoquinolin-7-yl)sulfonylamino]benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC(NS(=O)(=O)C=2C=C3C(Cl)=NC=C(Cl)C3=CC=2)=C1 YBTDADHCDXWFLF-UHFFFAOYSA-N 0.000 description 1
• XRNHHAKVBNYKLY-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamoperoxoate Chemical compound CC(C)(C)OOC(=O)NCCN XRNHHAKVBNYKLY-UHFFFAOYSA-N 0.000 description 1
• CSOJECDGWHHWRS-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylcarbamothioyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C CSOJECDGWHHWRS-UHFFFAOYSA-N 0.000 description 1
• IUUYANMOEMBTBV-UHFFFAOYSA-N tert-butyl pyrrolidin-1-ium-2-carboxylate;chloride Chemical compound Cl.CC(C)(C)OC(=O)C1CCCN1 IUUYANMOEMBTBV-UHFFFAOYSA-N 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• FYOWZTWVYZOZSI-UHFFFAOYSA-N thiourea dioxide Chemical compound NC(=N)S(O)=O FYOWZTWVYZOZSI-UHFFFAOYSA-N 0.000 description 1
• 230000002885 thrombogenetic effect Effects 0.000 description 1
• 229960000187 tissue plasminogen activator Drugs 0.000 description 1
• 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 108010065822 urokinase inhibitor Proteins 0.000 description 1
• 230000037314 wound repair Effects 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1